WO1994005335A1 - Nouvel analogue d'agent de contraste organique et procede de production - Google Patents

Nouvel analogue d'agent de contraste organique et procede de production Download PDF

Info

Publication number
WO1994005335A1
WO1994005335A1 PCT/US1992/007431 US9207431W WO9405335A1 WO 1994005335 A1 WO1994005335 A1 WO 1994005335A1 US 9207431 W US9207431 W US 9207431W WO 9405335 A1 WO9405335 A1 WO 9405335A1
Authority
WO
WIPO (PCT)
Prior art keywords
agent
analog
compound
set forth
contrast agent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1992/007431
Other languages
English (en)
Inventor
James L. Barnhart
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Molecular Biosystems Inc
Original Assignee
Molecular Biosystems Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US07/500,471 priority Critical patent/US5143715A/en
Priority claimed from US07/500,471 external-priority patent/US5143715A/en
Priority to US07/853,100 priority patent/US5250283A/en
Application filed by Molecular Biosystems Inc filed Critical Molecular Biosystems Inc
Priority to PCT/US1992/007431 priority patent/WO1994005335A1/fr
Priority to AU26451/92A priority patent/AU2645192A/en
Publication of WO1994005335A1 publication Critical patent/WO1994005335A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/54—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/25—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
    • C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/43—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/16—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/12—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton

Definitions

  • the present invention relates to organic contrast agent analogs and methods of making the analogs. More particularly, the present invention relates to a method of decreasing the toxicity of such agents through chemical modification.
  • contrast agents to visualize the biliary system. Because of the relative toxicity of these agents, these agents are being replaced in use by alternative imaging methodologies, such as
  • biliary contrast agents can still be quite useful.
  • a second issue with regard to these agents is the low rate of choleresis associated with biliary excretion of the agent. The low rate of choleresis increases the biliary concentration and thus
  • hydrophilic head portion that is, the -CO 2 H
  • hydrophobic tail that is, triiodo aniline moiety with an unsubstituted 5-position.
  • an organic contrast agent analog wherein the analog is an oral or intravenous media having the formula I:
  • the present invention further provides a method of making the organic contrast agent analog including the steps of forming the organic contrast agent analog having formulas I, II, or III and substituting or adding at least one flourine moiety to the analog.
  • Figures 1 and 2 are high resolution NMR proton spectrums
  • Figure 3 is a high resolution NMR fluorine spectrum
  • FIGS. 4 and 5 are mass spectrum analyses performed on TFA-IOP made in accordance with the present invention.
  • Figure 6 is a plotted curve comparing biliary concentration over time of IOP versus TFA- IOP;
  • Figure 7 is comparitive data of TFA-IOP and IOP plasma concentration versus time; and Figure 8 is comparative date of TFA-IOP and IOP biliary excretion concentration versus time.
  • an organic contrast agent analog made in accordance with the present invention has the following general formula I:
  • the agent includes a hydrophilic head ( side chain) and a hydrophilic tail (benzine ring) .
  • the flourine addition or substitution provides means for increasing the acidity of the agent and increasing the choleretic activity of the agent to render the agent less toxic.
  • oral cholecystographic contrast media which can be modified in accordance with the present invention are
  • the starting agent can be a cholangiographic or cholecystographic agent as stated above.
  • the agent can be of the oral or intravenous types. That is, the agent is iodinated such that it can be used as a biliary X-ray contrast agent for routine use to visualize hepatocytes gallbalder and the the biliary system.
  • the present invention is a chemically modified organic contrast agent analog which is rendered less toxic and more choleretic by the modification of the agent including additional fluorine functionalities on the agent, the fluorine functionalities rendering the agent more acidic and more choleretic.
  • amphophilic molecule such as a common organic contrast agent analog is rendered a stronger acid and is fully or at least more disassociated at
  • the biliary contrast agent is expected to move as a bolus, and anatomical details, such as the intrahepatic ducts, can be visualized in patients with good hepatocyte function.
  • the agent can be N-trifluoroacetyl-iopanoic acid or alpha-fluoro-N-trifluoroacidic-iopanoic acid.
  • the present invention further provides a method of making the organic contrast agent analog.
  • the method generally includes the steps of forming the organic contrast agent analog having the formulas I, II, or III and then increasing the acidity of the agent while increasing the choleretic activity of agent to render the agent less toxic by adding or subtituting flourine on the agent.
  • IOP cholecystographic agent iopanoic acid
  • TFA-IOP and IOP were eac.n administered intravenously to rats (100 umol/kg) in order to compare the biodistribution and excretion of the compound made in accordance with the present invention and the parent compound.
  • Tissues examined included liver, spleen, upper GI, lower GI, kidney, lung and heart. The length of each study was 90
  • liver concentrations 90 minutes post injection were 512 uM and 202 uM after IOP and TFA-IOP injection, respectively, while kidney
  • TFA-IOP reached a maximum concentration of .5 uM with the recovery of 40% of the injection dose during a 90 minute time period (see Figure 6).
  • the biliary concentration reached 10 mM with 18% of the injected does recovered during the 90 minute
  • Tables 1 through 5 summarizes the results of each experiment conducted.
  • Table 6 shows a more detailed analysis of the tissue concentration results with values such as total micromoles in tissue, percent of dose/gm, etc.
  • Tables 7 and 8 contain analysis of the bile excretion results.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Steroid Compounds (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Abstract

Un analogue d'agent de contraste est dérivé de façon à contenir des fractions de fluor. Un procédé de fabrication de cet analogue d'agent de contraste organique consiste à fluorer ledit analogue afin d'en accroître l'activité cholérétique et de le rendre moins toxique.
PCT/US1992/007431 1990-03-28 1992-08-31 Nouvel analogue d'agent de contraste organique et procede de production Ceased WO1994005335A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US07/500,471 US5143715A (en) 1990-03-28 1990-03-28 Organic contrast agent analog and method of making same
US07/853,100 US5250283A (en) 1990-03-28 1992-03-18 Organic contrast agent analog and method of making same
PCT/US1992/007431 WO1994005335A1 (fr) 1990-03-28 1992-08-31 Nouvel analogue d'agent de contraste organique et procede de production
AU26451/92A AU2645192A (en) 1990-03-28 1992-08-31 New organic contrast agent analog and method of making same

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US07/500,471 US5143715A (en) 1990-03-28 1990-03-28 Organic contrast agent analog and method of making same
US07/853,100 US5250283A (en) 1990-03-28 1992-03-18 Organic contrast agent analog and method of making same
PCT/US1992/007431 WO1994005335A1 (fr) 1990-03-28 1992-08-31 Nouvel analogue d'agent de contraste organique et procede de production

Publications (1)

Publication Number Publication Date
WO1994005335A1 true WO1994005335A1 (fr) 1994-03-17

Family

ID=27377094

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1992/007431 Ceased WO1994005335A1 (fr) 1990-03-28 1992-08-31 Nouvel analogue d'agent de contraste organique et procede de production

Country Status (2)

Country Link
US (1) US5250283A (fr)
WO (1) WO1994005335A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19731300C1 (de) * 1997-07-11 1999-01-21 Schering Ag Perfluoralkylgruppenhaltige Trijodaromaten, Verfahren zu deren Herstellung und deren Verwendung als Kontrastmittel
US8263040B2 (en) 2006-10-18 2012-09-11 Bayer Schering Pharma Ag Metal chelates having a perfluorinated PEG radical, processes for their preparation, and their use

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5650156A (en) * 1993-02-22 1997-07-22 Vivorx Pharmaceuticals, Inc. Methods for in vivo delivery of nutriceuticals and compositions useful therefor
US5665382A (en) * 1993-02-22 1997-09-09 Vivorx Pharmaceuticals, Inc. Methods for the preparation of pharmaceutically active agents for in vivo delivery
US6753006B1 (en) 1993-02-22 2004-06-22 American Bioscience, Inc. Paclitaxel-containing formulations
US20030133955A1 (en) * 1993-02-22 2003-07-17 American Bioscience, Inc. Methods and compositions useful for administration of chemotherapeutic agents
NZ262679A (en) * 1993-02-22 1997-08-22 Vivorx Pharmaceuticals Inc Compositions for in vivo delivery of pharmaceutical agents where the agents are contained in a polymeric shell
US20030068362A1 (en) * 1993-02-22 2003-04-10 American Bioscience, Inc. Methods and formulations for the delivery of pharmacologically active agents
WO1998053855A1 (fr) * 1997-05-30 1998-12-03 Alliance Pharmaceutical Corp. Procedes et appareil permettant de surveiller et de quantifier le mouvement d'un fluide
US7344702B2 (en) * 2004-02-13 2008-03-18 Bristol-Myers Squibb Pharma Company Contrast agents for myocardial perfusion imaging
US20030054042A1 (en) * 2001-09-14 2003-03-20 Elaine Liversidge Stabilization of chemical compounds using nanoparticulate formulations
WO2007085026A2 (fr) * 2006-01-20 2007-07-26 The Board Of Regents Of The University Of Texas System Compositions et procedes destines a traiter directement des tumeurs

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3446837A (en) * 1963-10-17 1969-05-27 Mallinckrodt Chemical Works 3 - (n - substituted - acylamino) - 2,4,6 - triiodophenyl fatty acid compounds
US3842124A (en) * 1970-12-15 1974-10-15 Bracco Ind Chimica Spa Orally administered contrast agents for cholecystography
US3856853A (en) * 1967-11-16 1974-12-24 Sterling Drug Inc Iodinated 5-substituted-1,3-benzenediacrylic and dipropionic acids
US3883578A (en) * 1970-10-02 1975-05-13 Schering Ag Radiopaque agents
US4094966A (en) * 1974-05-31 1978-06-13 Laboratoires Andre Guerbet Iodobenzene derivatives and x-ray contrast media containing the same
US4125709A (en) * 1974-10-04 1978-11-14 Mallinckrodt, Inc. Polyhydroxy-alkyl-3,5-disubstituted-2,4,6-triiodocarbanilates
US4132731A (en) * 1976-06-25 1979-01-02 Schering Aktiengesellschaft Novel iodized isophthalamic acid compounds
US4160015A (en) * 1976-08-19 1979-07-03 Mallinckrodt, Inc. 2,4,6-Triiodobenzoic acid derivatives and their use as x-ray contrast agents
US4395391A (en) * 1980-11-25 1983-07-26 Schering Aktiengesellschaft Unsymmetrically substituted dicarboxylic-acid-bis-(2,4,6-triiodo-anilides), their preparation, and x-ray contrast media containing same
US4474747A (en) * 1981-08-28 1984-10-02 Guerbet S.A. Process for increasing the tolerance of X-ray contrast media, and contrast media obtained thereby

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4073879A (en) * 1974-08-26 1978-02-14 University Of Illinois Foundation Brominated perfluorocarbon radiopaque agents
US4612185A (en) * 1984-10-15 1986-09-16 Mallinckrodt, Inc. Methods and compositions for enhancing magnetic resonance imaging
US4913853A (en) * 1984-11-14 1990-04-03 Mallinckrodt, Inc. Compositions useful for fluorine magnetic resonance imaging
US4951673A (en) * 1988-08-19 1990-08-28 Alliance Pharmaceutical Corp. Magnetic resonance imaging with perfluorocarbon hydrides
US5116599A (en) * 1989-07-31 1992-05-26 Johns Hopkins Univ. Perfluoro-t-butyl-containing compounds for use in fluorine-19 nmr and/or mri

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3446837A (en) * 1963-10-17 1969-05-27 Mallinckrodt Chemical Works 3 - (n - substituted - acylamino) - 2,4,6 - triiodophenyl fatty acid compounds
US3856853A (en) * 1967-11-16 1974-12-24 Sterling Drug Inc Iodinated 5-substituted-1,3-benzenediacrylic and dipropionic acids
US3883578A (en) * 1970-10-02 1975-05-13 Schering Ag Radiopaque agents
US3842124A (en) * 1970-12-15 1974-10-15 Bracco Ind Chimica Spa Orally administered contrast agents for cholecystography
US4094966A (en) * 1974-05-31 1978-06-13 Laboratoires Andre Guerbet Iodobenzene derivatives and x-ray contrast media containing the same
US4125709A (en) * 1974-10-04 1978-11-14 Mallinckrodt, Inc. Polyhydroxy-alkyl-3,5-disubstituted-2,4,6-triiodocarbanilates
US4132731A (en) * 1976-06-25 1979-01-02 Schering Aktiengesellschaft Novel iodized isophthalamic acid compounds
US4160015A (en) * 1976-08-19 1979-07-03 Mallinckrodt, Inc. 2,4,6-Triiodobenzoic acid derivatives and their use as x-ray contrast agents
US4395391A (en) * 1980-11-25 1983-07-26 Schering Aktiengesellschaft Unsymmetrically substituted dicarboxylic-acid-bis-(2,4,6-triiodo-anilides), their preparation, and x-ray contrast media containing same
US4474747A (en) * 1981-08-28 1984-10-02 Guerbet S.A. Process for increasing the tolerance of X-ray contrast media, and contrast media obtained thereby

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19731300C1 (de) * 1997-07-11 1999-01-21 Schering Ag Perfluoralkylgruppenhaltige Trijodaromaten, Verfahren zu deren Herstellung und deren Verwendung als Kontrastmittel
US8263040B2 (en) 2006-10-18 2012-09-11 Bayer Schering Pharma Ag Metal chelates having a perfluorinated PEG radical, processes for their preparation, and their use

Also Published As

Publication number Publication date
US5250283A (en) 1993-10-05

Similar Documents

Publication Publication Date Title
DE69424424T2 (de) Perfluoro-1h-1h-neopentyl-enthaltendes kontrastmittel und verfahren zu seiner verwendung
JP2548436B2 (ja) Ｎｍｒ−診断剤
DE69328550T2 (de) Verwendung von fulleren-derivaten in diagnostischen und/oder therapeutischen mitteln
DE69534990T2 (de) Kontrastmittel
DE69026384T2 (de) Perfluoro-t-butyl enthaltende verbindungen zur verwendung in fluor-19-nmr und/oder mri
EP0430863B1 (fr) Formateur de complexe lié à un polymère préparé par étapes, ses complexes et conjugats, procédé de préparation et substances pharmaceutiques les contenant
WO1994005335A1 (fr) Nouvel analogue d'agent de contraste organique et procede de production
EP0489869A1 (fr) Chelates metalliques d'hydroxy-aryle d'imagerie par resonnance magnetique nucleaire de diagnostic
DE69117084T2 (de) Chelatbildende Verbindungen und ihre Verwendung
JPH09503496A (ja) ヒドラジノ型ｎ▲下２▼ｓ▲下２▼キレート化剤
EP0606683B1 (fr) Agents pour la diagnose des maladies vasculaires
DE69432418T2 (de) Phosphonate- und nicht-phosphonate einheiten enthaltende polyamino-paramagnetische-chelate fuer anwendung in mri
US5811077A (en) Method of NMR imaging
DE60220765T2 (de) Komplexverbindungen aus paramagnetischem metall und phthalocyanin und kontrastmittel, bei dem diese verbindungen verwendet werden
EP1594851A1 (fr) Derives de benzene trimeres substitues de maniere macrocyclique
JP2901787B2 (ja) 核磁気共鳴造影剤
EP1307237B9 (fr) Complexes perfluoroalkyles a residus polaires, leur procede de fabrication et leur utilisation
US5143715A (en) Organic contrast agent analog and method of making same
Parkesh et al. Synthesis and evaluation of potential CT (computer tomography) contrast agents for bone structure and microdamage analysis
IE904319A1 (en) 10-(2'-Hydroxy-3'POLYOXAALKYL)-1,4,7-TRISCARBOXYMETHYL-¹1,4,7,10-TETRAAZACYCLODODECANE
DE69922052T2 (de) Immobilisierte marker-verbindungen und verfahren
DE10040380B4 (de) Verwendung von perfluoralkylhaltigen Metallkomplexen als Kontrastmittel im MR-Imaging zur Darstellung von Plaques
JP3404787B2 (ja) 新規ジエチレントリアミンペンタ酢酸誘導体、該誘導体と金属原子との錯化合物、及び該錯化合物を含む診断剤
DE69709700T2 (de) Kontrastmittel
KR100448100B1 (ko) 상자성 금속-프탈로시아닌 착화합물 및 이를 이용한영상화용 조영제

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA FI JP KR NO

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA